his project examines mechanisms of pathogenesis of diverse roups of obligately intracellular bacteria. Representative embers of different genera with varied sites of replication in he host cell are being examined. Coxiella burnetii, the tiological agent of Q fever replicates within the normally actericidal phagolysosome. Chlamydiae, in contrast, block hagosome-lysosome fusion and in doing so prevent their estruction and clearance from the host cell. Current interest enters on comparative aspects of intracellular survival of hese two agents. Initial events of chlamydia-host interaction ncluding attachment, internalization, inhibition of hagosome-lysosome fusion, and differentiation are being tudied with an emphasis on the role of disulfide mediated nteractions and exchange in the chlamydial life cycle. In ddition, we have identified two chlamydial proteins, present n the infectious stage of the chlamydial life cycle but absent rom the noninfectious form, that bind host cell surface rotein thus may potentially be involved in regulating host esponse to chlamydial infection. A different approach has een taken in the study of C. burnetii. This rickettsia ndergoes a virulent to avirulent transition termed phase ariation. The only components identified as structurally and ntigenically unique between phases were the ipopolysaccharides (LPS). As part of this investigation, we ave identified a previously unknown third LPS type ntermediate in structure between the virulent and avirulent PS. The organism possessing this unusual LPS was isolated rom the placental tissue of a guinea pig infected almost a ear previously with C. burnetii. Possible roles of this LPS ariation in the known capacity of C. burnetii for persistent r chronic infection of humans and animals are being examined.